Therapies for patients with coexisting heart failure with reduced ejection fraction and non-alcoholic fatty liver disease

Heart failure with reduced ejection fraction(HFrEF)and nonalcoholic fatty liver disease(NAFLD)are two common comorbidities that share similar pathophysiological mechanisms.There is a growing interest in the potential of targeted therapies to improve outcomes in patients with coexisting HFrEF and NAFLD.This manuscript reviews current and potential therapies for patients with coexisting HFrEF and NAFLD.Pharmacological therapies,including angiotensinconverting enzyme inhibitors/angiotensin receptor blockers,mineralocorticoids receptor antagonist,and sodium-glucose cotransporter-2 inhibitors,have been shown to reduce fibrosis and fat deposits in the liver.However,there are currently no data showing the beneficial effects of sacubitril/valsartan,ivabradine,hydralazine,isosorbide nitrates,digoxin,or beta blockers on NAFLD in patients with HFrEF.This study highlights the importance of considering HFrEF and NAFLD when developing treatment plans for patients with these comorbidities.Further research is needed in patients with coexisting HFrEF and NAFLD,with an emphasis on novel therapies and the importance of a multidisciplinary approach for managing these complex comorbidities.

Novel approaches for the development of peripheral nerve regenerative therapies

Schwann cells are the myelinating glial cells of the peripheral nervous system（PNS）.By establishing lipid-rich myelin sheaths around large-caliber axons,they ensure that electrical signal transmission is accelerated-a process referred to as saltatory signal propagation.Apart from this prominent physiological function,these cells also exert important pathophysiological roles in PNS injuries or dis- eases. In contrast to the central nervous system （CNS）, the adult PNS retains a remarkably high degree of intrinsic re- generation. As a consequence, transected axons and dam- aged myelin sheaths can be repaired and nerve functional- ity can be restored. This spontaneous regenerative capacity depends on （inter） actions of macrophages, neurons, and Schwann cells.

Pivotal role of exosomes in diagnosis and treatment of esophageal cancer in a new era of precision medicine

In this editorial we comment on the article published by Ning et al,“Role of exosomes in metastasis and therapeutic resistance in esophageal cancer”.Esophageal cancer(EC)represents a significant global health concern,being the seventh most common and sixth in terms of mortality worldwide.Despite the advances in therapeutic modalities,the management of patients with EC remains challenging,with a 5-year survival rate of only 25%and a limited eligibility for curative surgery due to its late diagnosis.Conventional screening methods are impractical for the early detection of EC,given their either invasive or insensitive nature.The advent of liquid biopsy,with a focus on circulating tumor cells,circulating tumor DNA,and exosomes,heralds a non-invasive avenue for cancer detection.Exosomes,small vesicles involved in intercellular communication,are highlighted as potential biomarkers for EC diagnosis and prognosis.Along with a diverse cargo encompassing various types of RNA,DNA molecules,proteins,and metabolites,exosomes emerge as key players in tumorigenesis,tumor development,and metastasis.Their significance extends to carrying distinctive biomarkers,including microRNAs(miRNAs),long non-coding RNAs,and circular RNAs,underscoring their potential diagnostic and prognostic value.Furthermore,exosomes may be utilized for therapeutic purposes in the context of EC treatment,serving as efficient delivery vehicles for therapeutic agents such as chemotherapeutic medicines and miRNAs.In this editorial we delve into the applications of exosomes for the early detection and treatment of EC,as well as the future perspectives.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

BRAF inhibitor:a novel therapy for ameloblastoma in mandible

Ameloblastoma is a benign but locally aggressive odontogenic neoplasm that accounts for 10% of all tumors arising in the mandible and maxilla (1). Eighty percent of ameloblastomas arise in the mandible, and they are usually found in young adults. It frequently recurs if not adequately

Novel triple therapy for hemorrhagic ascites caused by endometriosis:A case report

BACKGROUND Massive hemorrhagic ascites caused by endometriosis is exceedingly rare,and the treatment strategy remains controversial.Here,we report a case of endometriosis with massive hemorrhagic ascites treated with a novel triple therapy including conservative surgery,gonadotropin-releasing hormone agonist,and then dienogest.CASE SUMMARY A 28-year-old nulliparous patient was admitted to Shengjing Hospital of China Medical University,and exploratory laparoscopy was performed.A total of 9500 mL of brown ascites was aspirated from the pelvic cavity,the bilateral ovaries strongly adhered to the posterior of the uterus and were fixed to the pelvic floor,and endometriotic cysts were not observed in either ovary.The pelvic and abdominal peritonea were covered with patchy red,white,and brown endometriotic lesions and defects.Partial surgical resection of endometriotic lesions on the peritoneum was performed while we simultaneously collected multiple peritoneal biopsies.The final pathological diagnosis was endometriosis coupled with hemorrhagic necrotic tissue.CONCLUSION Postoperative injection of gonadotropin-releasing hormone agonist was provided three times,followed by dienogest administration,and we will continue to follow up with this ongoing treatment.

Bone flare after initiation of novel hormonal therapy in patients with metastatic hormone-sensitive prostate cancer:A case report

BACKGROUND The 2020 European Association of Urology prostate cancer guidelines recommend androgen deprivation therapy(ADT)in combination with apalutamide and enzalutamide,a new generation of androgen receptor antagonists,as first-line therapy.A decrease in prostate-specific antigen(PSA)levels may occur in the early stages of novel hormonal therapy;however,radionuclide bone imaging may suggest disease progression.During follow-up,PSA,radionuclide bone imaging,and prostate-specific membrane antigen(PSMA)positron emission tomography–computed tomography(PET-CT)are needed for systematic evaluation.CASE SUMMARY We admitted a 56-year-old male patient with metastatic hormone-sensitive prostate cancer.Initial radionuclide bone imaging,magnetic resonance imaging(MRI),and PSMA PET-CT showed prostate cancer with multiple bone metastases.Ultrasound-guided needle biopsy of the prostate revealed a poorly differentiated adenocarcinoma of the prostate with a Gleason score:5+4=9.The final diagnosis was a prostate adenocarcinoma(T4N1M1).ADT with novel hormonal therapy(goseraline sustained-release implant 3.6 mg monthly and apalutamide 240 mg daily)was commenced.Three months later,radionuclide bone imaging and MRI revealed advanced bone metastasis.However,PSMA PET-CT examination showed a significant reduction in PSMA aggregation on the bone,indicating improved bone metastases.Considering that progressive decrease in the presenting lumbar pain,treatment strategies were considered to be effective.CONCLUSION ADT using novel hormonal therapy is effective for treating patients with prostate adenocarcinoma.Careful evaluation must precede treatment plan changes.

Stem cell therapy in ocular pathologies in the past 20 years

Stem cell therapies are successfully used in various fields of medicine.This new approach of research is also expanding in ophthalmology.Huge investments,resources and important clinical trials have been performed in stem cell research and in potential therapies.In recent years,great strides have been made in genetic research,which permitted and enhanced the differentiation of stem cells.Moreover,the possibility of exploiting stem cells from other districts(such as adipose,dental pulp,bone marrow stem cells,etc.)for the treatment of ophthalmic diseases,renders this topic fascinating.Furthermore,great strides have been made in biomedical engineering,which have proposed new materials and threedimensional structures useful for cell therapy of the eye.The encouraging results obtained on clinical trials conducted on animals have given a significant boost in the creation of study protocols also in humans.Results are limited to date,but clinical trials continue to evolve.Our attention is centered on the literature reported over the past 20 years,considering animal(the most represented in literature)and human clinical trials,which are limiting.The aim of our review is to present a brief overview of the main types of treatments based on stem cells in the field of ophthalmic pathologies.

Viral hepatitis:A narrative review of hepatitis A–E

Viral hepatitis continues to be a major health concern leading to hepatic decompensation ranging from acute hepatitis to cirrhosis and hepatocellular carcinoma.The hepatic and extrahepatic manifestations are not only debilitating but also associated with a significant economic burden.Over the last two decades,the field of virology has made significant breakthroughs leading to a better understanding of the pathophysiology of viral hepatitis,which in turn has led to new therapeutic options.The advent of direct-acting antiviral agents changed the landscape of hepatitis C virus(HCV)therapy,and new drugs are in the pipeline for chronic hepatitis B virus(HBV)treatment.There has also been a significant emphasis on screening and surveillance programs,widespread availability of vaccines,and linkage of care.Despite these efforts,significant gaps persist in care,and there is a pressing need for increased collaboration and teamwork across the globe to achieve a reduction of disease burden and elimination of HBV and HCV.

CRISPR accelerates the cancer drug discovery

Emerging cohorts and basic studies have associated certain genetic modifications in cancer patients,such as gene mutation,amplification,or deletion,with the overall survival prognosis,underscoring patients’genetic background may directly regulate drug sensitivity/resistance during chemotherapies.Understanding the molecular mechanism underpinning drug sensitivity/resistance and further uncovering the effective drugs have been the major ambition in the cancer drug discovery.The emergence and popularity of CRISPR/Cas9 technology have reformed the entire life science research,providing a precise and simplified genome editing tool with unlimited editing possibilities.Furthermore,it presents a powerful tool in cancer drug discovery,which hopefully facilitates us with a rapid and reliable manner in developing novel therapies and understanding the molecular mechanisms of drug sensitivity/resistance.Herein,we summarized the application of CRISPR/Cas9 in drug screening,with the focus on CRISPR/Cas9 mediated gene knockout,gene knock-in,as well as transcriptional modification.Additionally,this review provides the concerns,cautions,and ethnic considerations that need to be taken when applying CRISPR in the drug discovery.

Consensus on safety management of novel hormonal therapy for advanced prostate cancer

Prostate cancer(PCa)is one of the most prevalent malignant tumors in men,accompanied by high incidence and mortality rates.Novel hormonal therapy(NHT)has emerged as the primary treatment for advanced PCa,providing noticeable clinical benefits.However,the diverse range of adverse events(AEs)associated with NHT may influence both treatment efficacy and patients'quality of life.In light of the latest international clinical research evidence and recommendations from domestic and foreign guidelines,this consensus aims to provide a comprehensive overview of the common AEs experienced during NHT for advanced PCa patients.Additionally,it seeks to develop a hierarchical approach to more efficiently manage AEs,presenting valuable insights for clinical medication and adverse reaction management.

Barriers to achieving a cure in lymphoma

Lymphoma is a diverse disease with a variety of different subtypes,each characterized by unique pathophysiology,tumor microenvironment,and underlying signaling pathways leading to oncogenesis.With our increasing understanding of the molecular biology of lymphoma,there have been a number of novel targeted therapies and immunotherapy approaches that have been developed for the treatment of this complex disease.Despite rapid progress in the field,however,many patients still relapse largely due to the development of drug resistance to these therapies.A better understanding of the mechanisms underlying resistance is needed to develop more novel treatment strategies that circumvent these mechanisms and design better treatment algorithms that personalize therapies to patients and sequence these therapies in the most optimal manner.This review focuses on the recent advances in therapies in lymphoma,including targeted therapies,monoclonal antibodies,antibody-drug conjugates,cellular therapy,bispecific antibodies,and checkpoint inhibitors.We discuss the genetic and cellular principles of drug resistance that span across all the therapies,as well as some of the unique mechanisms of resistance that are specific to these individual classes of therapies and the strategies that have been developed to address these modes of resistance.